The Vo2max and the Central Governor: a Different Understanding

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THE VO2MAX AND THE CENTRAL GOVERNOR: A DIFFERENT UNDERSTANDING

Timothy David Noakes UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town and Sports Science Institute of South Africa, Boundary Road, Newlands, 7700, South Africa

ABSTRACT

In 1923, Nobel Laureate A.V. Hill introduced his cardiovascular/ anaerobic/ catastrophic model of human exercise performance. According to this model, maximal

exercise testing for the measurement of the maximum oxygen consumption (VO2max) terminates when the maximum rate of oxygen delivery to the exercising muscles is less than their peak rate of oxygen demand. As a result skeletal muscle anaerobiosis develops, causing fatigue and the termination of exercise. The weakness of this interpretation is that it is “brainless” since it excludes any role for the brain in determining maximal exercise performance. Yet without the brain, there can be no skeletal muscle recruitment, without which exercise cannot occur. The analogy is a racing car: A racing car filled with petrol will not move off the starting grid until the brain of the racing driver starts the car‟s engine, engages first gear and applies pressure to the car‟s accelerator. The role of the brain in exercise performance is identical; until the muscles are recruited by the motor cortex, they will not function; without increasing skeletal muscle recruitment, the oxygen consumption and cardiac output cannot rise. Thus it is the level of skeletal muscle recruitment that must determine the athlete‟s maximal work rate as well as the extent to

which the cardiac output and oxygen consumption rise during the VO2max test. Remarkably the Hill model has instilled the reverse doctrine specifically that the cardiac output, not the level of skeletal muscle recruitment, determines the work output of the muscles. In this chapter I present 6 biological predictions of the Hill model of maximal exercise performance that have been disproven specifically that (i) the “plateau

phenomenon” does not occur in 100% of subjects during VO2max testing; (ii) skeletal muscle anaerobiosis does not occur during maximal exercise; (iii) the cardiac output does 80 Timothy David Noakes

not show a “plateau phenomenon” nor (iv) are all available motor units activated in the

exercising limbs of all subjects during VO2max testing; (v) fatigue does not always develop at the same level of “fatiguing” metabolites; and (vi) fatigue is never absolute.

Instead the evidence is that the VO2max test is a submaximal test that is terminated by the brain when less than 100% of the motor units in the exercising limbs have been recruited.

The protected variable that triggers this anticipatory termination of the VO2 max test is currently unknown but may well relate to changes in cerebral oxygenation.

INTRODUCTION

On the basis of his interpretation that fatigue is caused by anaerobiosis in the exercising muscles as a result of the development of myocardial ischaemia, in 1923 Professor Archibald

Vivian Hill introduced the concept of the maximum oxygen consumption (VO2max) into the exercise sciences (Chapter 1). In 1955 H.L. Taylor and colleagues[1] established this concept by stating that: “The classic work of Hill has demonstrated that there is an upper limit to the capacity of the combined respiratory and cardiovascular systems to transport oxygen to the muscles. There is a linear relationship between oxygen intake and work rate until the maximum oxygen intake is reached. Further increases in workload beyond this point merely result in an increase in oxygen debt and a shortening of the time in which the work can be performed”. These scientists were also the first to describe the concept that would become known as the “plateau phenomenon”: “Each day the (running) speed was increased until the oxygen uptake during the standard collection time reached a plateau”. In the past 50 years few have felt it necessary to question the veracity of these concepts. Those who have dared[2-5], have usually attracted a dismissive response[5-15] suggesting that new ideas are not always welcome in the exercise sciences. In a recent publication Mitchell and Saltin[16] provided their most current interpretation of Hill‟s contribution to our understanding of the physiological basis for the VO2max: “It is noteworthy that although well-designed treadmills were available, Hill preferred walking and running in the field or on the track for his experiments. To determine the velocity of the runner, he developed a sophisticated electromagnetic system that provided split times for every 25 yards. In the experiments on Hill himself, a levelling off in VO2 was observed, not as a function of increasing speed of running, but with the time at the highest velocity, which was 260 meters.min-1[17]. Noakes has challenged whether Hill actually demonstrated a plateau in VO2 and thus had measured a true VO2max[3]. Hill appears to have accomplished this in the experiments conducted on himself; but more importantly, he was the one who conceived the physiological meaning of maximal VO2.” Elsewhere [18, 19] I have provided the contradictory evidence which shows that Hill was absolutely convinced that his model of the physiological factors limiting the VO2max was beyond doubt. So why would he have considered it necessary to “prove” this theory by showing the presence of the “plateau phenomenon”? In his mind he had already done that. Only later, when his theory began to be questioned for the first time, did a modern generation of scientists feel the urgent need to “prove” that Hill‟s ideas were correct by attempting to show that the “plateau phenomenon” or some equivalent [10, 11, 15, 20, 21] always causes the termination of exercise in all VO2max tests (as is required by the Hill model). The VO2MAX and the Central Governor 81

In fact, as argued in Chapter 1, the real test of a maximal effort according to the Hill model must be the development of myocardial ischaemia and cardiac failure, according to Hill‟s idea that: “When the oxygen supply becomes inadequate, it is probable that the heart rapidly begins to diminish its output, so avoiding exhaustion”[22]. However the well-established finding that myocardial ischaemia does not occur during maximal exercise in healthy subjects [23] disproves this component of Hill‟s model. Not surprisingly protagonists of this model chose to ignore this inconvenient finding, continuing rather to argue that it is the presence of a “plateau phenomenon”, defined in at least 10 different ways [24] that proves the model. Whereas I argue that according to the Hill model the sole proof that a VO2max test is “truly maximal” is the development of myocardial ischaemia. Or alternatively that exercise terminates only after all the available motor units in the active limbs have been recruited (Chapter 1). Mitchell and Saltin[16] included a diagram, redrawn here as Figure 1, which explained why they believe the VO2max is limited by the maximum cardiac output and the maximum systemic arterio-venous oxygen difference. According to this (Hill) model, three factors, namely cardiovascular function (specifically the maximum cardiac output), the blood haemoglobin concentration, and the extent to which oxygen is extracted from the arterial blood by the active muscles determine the magnitude of the VO2max. The focus of this chapter is to argue that the model depicted in Figure 1 is only valid if exercise is indeed limited by a failure of oxygen delivery to the exercising muscles as Hill had presumed in 1923 but which, I argue, his data did not ever prove [4, 18, 24, 25].

Maximal oxygen uptake

Maximal cardiac output Maximal systemic a-VO2 difference

Maximal Maximal stroke Maximal arterial O2 Minimal mixed heart rate volume content venous O2 content

Maximal Minimal Hemoglobin % O2 Redistribution Extraction end-diastolic end-systolic concentration saturation of blood of O2 volume volume flow

Figure 1. The physiological factors that determine or “limit” the maximum oxygen consumption

(VO2max) according to the traditional A.V. Hill model. After Mitchell and Saltin [16]. 82 Timothy David Noakes

MOTOR UNIT RECRUITMENT Number Frequency

1.RESPIRATION 4.CENTRAL CIRCULATION Maximum ventilation Coronary blood flow Alveolar ventilation: Myocardial contractility perfusion ratio Cardiac output Alveolar – arterial O2 diffusion Pulmonary capillary pressure

Haemoglobin – O2 affinity Systemic blood pressure [Haemoglobin]

2.PERIPHERAL CIRCULATION 3.MUSCLE CONTRACTION / METABOLISM Muscle blood flow Muscle mass Muscle vasodilatory capacity Muscle fiber type Muscle capillary density Muscle contractility Capillary O2 diffusion Mitochondria – size and number Mitochondrial O2 extraction [Myoglobin] Haemoglobin-O2 affinity Energy stores Flow to non-exercising regions Substrate delivery Hormonal response

Figure 2. The popular diagram showing the four physiological systems (respiration, peripheral circulation, central circulation and muscle contraction/metabolism) that are believed to “limit” the

VO2max according to the traditional A.V. Hill model. The missing element in this diagram is the central nervous system. Without the recruitment of sufficient motor units in the limbs, movement and hence exercise is not possible. Without an increased skeletal muscle recruitment, there can be no increase in VO2. In which case the “VO2max” is limited by the absence of the brain.

4. CENTRAL CIRCULATION 1. RESPIRATION

Pi ATP ADP 3. MUSCLE CONTRACTION / 2. PERIPHERAL METABOLISM CIRCULATION ADP Pi

Figure 3. According to the Hill model the function of the cardiorespiratory system and skeletal muscle metabolism (A) is to maximize the rate of ATP production (B) so that the rate of force production by the muscle is also maximal. The VO2MAX and the Central Governor 83

The core belief of the Hill model is that the capacity of the heart and cardiovascular system to provide oxygen to the exercising muscles determines the exercise performance. As P.O. Astrand wrote in his PhD thesis in 1952: “The working capacity of the heart may determine that of the muscles” [26]. Or as Levine has written more recently: “the primary distinguishing characteristic of elite endurance athletes that allows them to run fast over prolonged periods of time is a large, compliant heart with a compliant pericardium that can accommodate a lot of blood, very fast, to take advantage of the Starling mechanism to generate a large stroke volume”[6] (p. 31). This theory has been expanded somewhat into a popular diagram (Figure 2) which proposes that factors relating to respiration, peripheral circulation, central circulation and muscle metabolism ultimately determine human exercise capacity. According to this theory, the key function of these systems is to ensure that there is a maximal rate of ATP generation in the muscles. As a consequence it is believed that the critical determinant of the amount of work that the muscles can perform is the rate at which the cardio-respiratory and metabolic systems (A) can supply ATP (B) to fuel the actin and myosin cross-bridge cycles in the exercising muscles (Figure 3). But the ignored elephant in this particular sitting room is the absence of the brain. For without the brain, the depicted human would be unable to stand, let alone exercise vigorously. An intriguing question is: Why has it taken so long for anyone to detect the obvious omission from this diagram? Figure 4 explains why this model cannot be the truth. For the simple reason that the provision of ATP does not activate the cross-bridge cycle; rather something more than just ATP is required to induce a muscle contraction (which can then utilize the ATP so generously provided by these other systems). The analogy might be to a racing car that has a full tank of petrol. Even with a full tank a racing car cannot begin the race unless a driver starts the engine, engages first gear and applies his foot forcibly to the accelerator.

1. RESPIRATION 4. CENTRAL CIRCULATION

Pi ++ ATP ADP Ca

3. MUSCLE CONTRACTION / 2. PERIPHERAL METABOLISM CIRCULATION ADP Pi

Figure 4. Skeletal muscle contraction (B) is initiated by calcium release from the sarcoplasmic reticulum which is dependent on the functioning of intact central and peripheral nervous systems (A). The cardiorespiratory and skeletal muscle metabolic systems (C) function to generate ATP at rates sufficient to cover the demands generated by skeletal muscle recruitment directed by the central nervous system. 84 Timothy David Noakes

In the analogy to skeletal muscle contraction, the driver is the central nervous system (Figure 4). His action in pressing the accelerator is equivalent to the neurally-regulated release of calcium from the sarcoplasmic reticulum within the muscle fibers. The arrival of calcium at the myofilaments allows the cross-bridge cycle to occur; only then is ATP required (in proportion to the number of cross-bridges that are formed) to allow each cross-bridge to relax before another cross-bridge can be formed. Thus the amount of ATP required to sustain this activity is a function of the exercising workload. But it is not the ATP that drives muscle contraction. The analogy is complete when it is realized that the function of the driver's brain is to ensure that the racing car completes the race safely without driving so fast that it leaves the race track destroying the car and potentially also the driver. The brain does this by always insuring that it recruits just sufficient motor units (and hence muscle fibers) in the driver‟s right calf muscles so that the pressure on the accelerator always produces the correct car speed, appropriate for each segment of the race track and for each moment of the race. The Central Governor Model (CGM) predicts that during exercise the brain acts identically, insuring that just sufficient motor units are always activated in the exercising limbs to ensure that the exercise can be completed safely. The brain achieves this by modifying behavior in anticipation to ensure that the brain, the body and ultimately the human species survive. The brain of the athlete, like that of the racing car driver, is interested ultimately in survival. As a result all athletic performances are submaximal since the only truly maximal athletic performance would be the one that causes the athlete‟s death. As a result, the missing factor in the traditional diagram of the factors limiting exercise performance is the role of the brain in directing the extent of skeletal muscle recruitment on a moment-to-moment basis during exercise. I argue that the goal of this control must be to insure the protection of whole body homeostasis.

THE SIX PHYSIOLOGICAL PREDICTIONS OF THE A.V. HILL MODEL

Two key concepts in science are that (i) we can interpret scientific information, including new data, only according to a conceptual model of how we think a particular system works. The value of these models is that they make predictions which can then be tested in appropriate experiments. But (ii) a conceptual model must be changed as soon as evidence that it does not predict becomes available. Once there is even a single finding that is not predicted by a particular model, that model must be either modified or discarded, or else it becomes a “creaking and ugly edifice” [3]. It is my contention that the A.V. Hill model makes at least 6 predictions, all of which have been disproven. As a result, I continue to argue that the A.V. Hill model needs to be retired and replaced by a model that better explains all (not just some) of the relevant findings in the exercise sciences. The six predictions of the A.V. Hill cardiovascular/anaerobic/catastrophic (CAC) model (Chapter 1) that in our view [24] have been disproven are the following:

The VO2MAX and the Central Governor 85

First Disproven Prediction of A.V. Hill’s CAC Model

A stable, non-rising “plateau phenomenon” does not occur in 100% of subjects causing termination of the VO2 Max test. Hill‟s explanation of the physiological events that cause the termination of maximal exercise was, as described in the companion chapter (Figure 4 in Chapter 1), unambiguous. He believed that the development of myocardial ischemia, limited by a governor that protected the heart by reducing acutely its pumping capacity, led to skeletal muscle anaerobiosis, lactic acidosis and the impairment of skeletal muscle relaxation. Since this description is so precise, it should be easily detectable by the following sequence of events: (i) The development of acute myocardial ischaemia with the diagnostic symptoms of angina pectoris followed by (ii) an abrupt plateau in cardiac output and in oxygen consumption (VO2), leading to (iii) a fall in cardiac output and VO2 as progressive cardiac failure develops consequent to (iv) continuing myocardial ischaemia. But the reality is that the only “evidence” for this sequence of events is that, in a certain proportion of tested subjects, the VO2 does not increase linearly up to the point of exercise termination. This classic response was depicted in the highly influential paper by Mitchell and Blomqvist published in the New England Journal of Medicine in 1971 (Figure 5; see also Figure 2 in Chapter 1). These figures suggest that the oxygen consumption exhibits the “plateau phenomenon” for at least 2 workloads before the termination of any bout of progressive maximal exercise.

4 5 6

) 4 1 - 3 3

2 (l.min

2 2 2 1 VO 1 0 150 3 4 1 2

SV (ml)SV 100 0 4

) 200 3 1 - 2 150 1 min 0 4

HR (beats.HR 100

Absenceof data

) 1

- 20 2 15 1 10 0

CO (l.min CO 5

0 1 2 3 4 VO (l.min-1) 2

Figure 5. An original diagram [55] of the cardiovascular changes during exercise up to the point at which the VO2max is achieved failed to indicate the changes in stroke volume, heart rate and cardiac output that, according to the Hill model, must occur subsequent to the achievement of VO2max. 86 Timothy David Noakes

Myocardial ischaemia

) 1

- 1.0 The VO2max test will 0.5 CF (l.min CF always

terminate )

1 after the - 20 development 15 of angina 10 CO (l.min CO pectoris and

will induce a

) 1 - 3 progressive

2 cardiac (l.min

2 2 failure

1 VO

0 1 2 3 4 5 6 Work load

Figure 6. If the cardiac output limits the VO2max, then this must be because there is first a plateau in coronary blood flow which induces myocardial ischaemia, angina pectoris and a progressive cardiac failure followed by a falling VO2.

It is interesting that the text accompanying that figure makes no reference to the changes in cardiovascular function that must happen once the “plateau phenomenon” has occurred. In a previous paper[4] I argued that the cause of the plateau in VO2 must be a plateau in cardiac output caused by a plateau in coronary blood flow leading to myocardial ischaemia and a progressive cardiac failure (Figure 6). According to this interpretation, faithful to Hill‟s original interpretation, the VO2max test must always terminate after the development of myocardial ischaemia, angina pectoris and a progressive cardiac failure (Chapter 1). One of the more interesting studies that has relevance to this theory is shown in Figure 7.

In that study [20] the change in VO2 immediately preceding the termination of the test was studied in approximately 70 subjects. In 28% of the tests, the subjects‟ VO2 rose exponentially immediately prior to the termination of the test (Figure 7; top panel). In another

55% of tests, the subjects‟ VO2 rose linearly up to the point of exhaustion (Figure 7; middle panel). In only 12 subjects, that is in only 17% of the total study population, did the VO2 appear to reach a “plateau” prior to the termination of exercise (Figure 7; bottom panel). The authors did not report that any test terminated after the development of myocardial ischaemia and angina pectoris.

Thus these data provided by a group with a strong belief that the VO2max is determined by a failure of oxygen delivery to the muscles [20, 21, 27], found that more than 80% of these maximal exercise tests terminated without any evidence for a “plateau phenomenon”, however liberally defined. According to the logic applied by A.V. Hill, this finding must mean that more than 80% of these tests did not terminate as a result of skeletal muscle The VO2MAX and the Central Governor 87 anaerobiosis consequent to the development of a maximal cardiac output and myocardial ischaemia. But instead of acknowledging this inconvenient truth, the authors spun the finding as evidence that it is unnecessary to demonstrate the “plateau phenomenon” to prove that a

“true” VO2max had been achieved. As one of the reviewers of that paper I encouraged the authors to add some discussion of how their data disprove this key prediction of the A.V. Hill model. Not unsurprisingly the authors were allowed to publish their paper in one of the world‟s leading journals of physiology without any reference to this important conclusion, which must indicate that there is a publication bias favoring those articles that appear to support the predictions of the A.V. Hill model. In our review [24] of the limitations of the A.V. Hill model, we analyzed 33 studies that have reported the percentage of VO2max tests that terminated with or without evidence for a “plateau phenomenon”. Considering that the physiological events causing the “plateau phenomenon” are supposed to be absolutely specific (Figure 4 in Chapter 1) – the development of a maximum cardiac output leading to an abrupt failure of oxygen delivery to the exercising muscles – it is surprising that there are at least 10 different definitions of how these events can be identified. Of a total of 1978 individual VO2max tests reported in the literature by 2004, 44% showed evidence for some form of “plateau phenomenon” as defined by one or more of these 10 different criteria.

4 n = 19 (28%)

) 1

- n = 40 (55%)

(L.min 2

VO 0 4

n = 12 (17%)

0 0 1200 Time

Figure 7. The study of Day et al. [20] found that there were 3 different patterns of change in VO2 preceding the termination of exercise during testing for the VO2max. In 28% of subjects (top panel) the

VO2 rose exponentially immediately prior to exercise termination; in 55% the rise was linear (middle panel) and in only 17% was there evidence for a “plateau phenomenon” (bottom panel). 88 Timothy David Noakes

The A.V. Hill’s Cardiovascular/Anaerobic/ Central Catastropic Model (CACM) of Exercise Governor Physiology and Athletic Performance Model (CGM)

1 The presence of 2 The absence of a 6 Muscle 7 Muscle a plateau plateau indicates anaerobiosis anaerobiosis indicates that adequate muscle ? always limits does not limit muscle oxygenation maximal exercise maximal anaerobiosis during maximal performance with exercise occurs during exercise. or without a performance in maximal exercise. plateau. all subjects. EITHER OR 3 Hill, Long and 5 However the Lupton showed plateau is not that the plateau always present develops during during maximal 4 Hence muscle maximal exercise. anaerobiosis exercise. limits maximal exercise performance.

Figure 8. If skeletal muscle anaerobiosis identified by the presence of the “plateau” phenomenon causes the termination of exercise, then the absence of this phenomenon in some must indicate that factors other than skeletal muscle anaerobiosis cause the termination of exercise in those subjects.

Aside from the obvious comment that a physiological event which is supposed to be so specific should produce a characteristic and easily identifiable physiological response, specifically an abrupt ceiling in the rate of whole body VO2 measured by sampling the expired air, this finding raises an even more important question: What causes the termination of exercise in the ~50% of subjects who do not show any evidence for a “plateau phenomenon”, however defined, immediately prior to the termination of the VO2max test? According to the predictions of the A.V. Hill model, this cannot be due to a limiting cardiac output, skeletal muscle anaerobiosis, lactic acidosis and a failure of skeletal muscle relaxation. But if these (patho) physiological changes do not cause the termination of exercise, then the obvious question is: What does? Figure 8 first published in 1998 and since largely ignored, compares the interpretation of these data according to either the A.V. Hill model or the CGM. The key argument is that the absence of a “plateau phenomenon” must indicate the presence of adequate muscle oxygenation during maximal exercise. For if this is not true, then neither is the converse. And if the converse is not true, then the A.V.Hill model is not valid.

Thus if a “plateau” is not present at the termination of a VO2max test, then the cause of that exercise termination cannot be explained by the A.V. Hill model since that model requires that myocardial failure and skeletal muscle anaerobiosis must always occur before the exercise terminates. In contrast, the CGM explains the absence of the “plateau The VO2MAX and the Central Governor 89 phenomenon” as evidence that a factor or factors other than skeletal muscle anaerobiosis must cause the termination of maximal exercise in those subjects. According to the CGM, the presence of the “plateau phenomenon” could be explained by a number of phenomena other than simply the development of skeletal muscle anaerobiosis. For example, it could indicate an increased reliance on oxygen-independent metabolism in anticipation that the exercise is about to terminate (so that there is no need to further increase oxygen utilization). This fits with the idea that the central governor has the capacity to act in an anticipatory manner (Chapter 1).

Second Disproven Prediction

Skeletal muscle anaerobiosis does not occur during maximal exercise in humans. The second absolute prediction of the A.V. Hill model is that skeletal muscle anaerobiosis must be present at exhaustion in 100% of subjects. Remarkably, two of the leading scientists studying skeletal muscle oxygenation during maximal exercise have both concluded that skeletal muscle anaerobiosis does not occur during maximal exercise even when maximal exercise is performed in hypoxia. Thus in 1998 Richardson and colleagues [28] concluded that: “…skeletal muscle cells do not become anaerobic … since intracellular PO2 is well preserved at a constant level even at maximal exercise” and that “average intracellular PO2 remains above PO2crit even at maximal exercise in hypoxia”. Similarly, Mole et al. [29] concluded that: “…O2 availability is not limiting VO2 during exercise”. Perhaps not surprisingly these inconvenient conclusions of such leading scientists have been ignored since they disprove the foundation belief on which A.V. Hill built his model. Instead what seems to be favored is that which Fletcher and Hopkins [30] (Chapter 1) wrote in 1907: “Lactic acid is spontaneously developed under anaerobic conditions…”.

Third Disproven Prediction

The cardiac output does not show a “plateau phenomenon” in 100% of subjects at the termination of the VO2 Max test. The third absolute requirement of the A.V. Hill model is that the cardiac output must always be maximal at fatigue since the heart is merely the slave to the oxygen demands of the exercising muscles. As a consequence the heart must pump to its maximum capacity whenever fatigue occurs in order to maximize oxygen delivery to the oxygen-starved muscles. But a number of studies have established that exercise frequently terminates before the cardiac output or stroke volume reaches a “plateau” or maximum value[31]. The notable exceptions are a series of studies many from the same laboratory, which show a plateau in cardiac output during high-intensity exercise [32]. In contrast scientists from another laboratory who consistently argue that oxygen limits exercise performance [33-35] are unable to find a plateau in cardiac output during maximal exercise [36]. Yet they nevertheless still conclude that “in healthy humans VO2max is limited by cardiac output and skeletal muscle blood flow”. 90 Timothy David Noakes

But if the cardiac output does indeed “plateau” during maximal exercise, then this should cause myocardial ischaemia as it does in persons with coronary artery stenosis [37], for the reasons described in Chapter 1. None of the subjects in the studies apparently showing a “plateau” in cardiac output reported the development of angina pectoris which must occur if cardiac output reaches a true maximum. In one study the central venous pressure reportedly rose [38]. This is surprising since this indicates the onset of cardiac failure. Yet if cardiac failure is indeed the reason why maximal exercise terminates in young, healthy subjects, as predicted by the A.V. Hill model, then surely other researchers would also have reported that finding sometime in the past 80 years? However the most striking and well documented example of a failure to achieve a maximum cardiac output at exercise termination occurs during maximal exercise in extreme hypoxia. Under those conditions the well-described “lactate paradox” of high altitude (hypoxia) occurs [39]. In this condition, blood lactate concentrations are low at exhaustion. Less well appreciated is the “cardiac output paradox” of high altitude in which both the cardiac output and heart rate are also sub-maximal at exhaustion. A popular explanation is that the heart becomes progressively more hypoxic at increasing altitude; its function fails [40] and, as a consequence, it is unable to provide enough oxygen to the exercising muscles. But there is clear evidence that the heart is not hypoxic during maximum exercise at altitude [33, 34, 41-43]; thus this explanation whilst convenient, is simply wrong. A more likely explanation [39] is that the extent of skeletal muscle recruitment becomes progressively less at increasing altitude [44] or increasing levels of induced hypoxia[45] so that paradoxically low cardiac outputs and blood lactate concentrations are simply the result of reduced levels of skeletal muscle recruitment allowed by the brain at increasing altitude or greater levels of hypoxia. The finding that the “maximal” cardiac output in hypoxia is sub-maximal is especially paradoxical according to the A.V. Hill model. This is because the cardiac output should be as high or higher during maximum exercise in hypoxia than in normoxia so that the delivery of blood with a lower oxygen content can be maximized. Rather the more reasonable explanation is that skeletal muscle recruitment is reduced at altitude; this reduces the oxygen demands of the exercising muscles as well as the rates of skeletal muscle lactate production and release. Figure 9 explains why I think so many find it difficult to understand this paradox. This figure shows the cardiac output/work rate relationship in an experiment reported by Calbet and colleagues [34]. The traditional (Hill) method of interpreting this figure is to assume that the cardiac output drives the work rate; in other words that A, a greater cardiac output, causes B, the higher work rate. But the CGM argues that it is the brain‟s feed-forward recruitment (C) of the motor units in the exercising limbs that determines the work rate, the oxygen demand of the exercising muscles and hence the cardiac output (A). According to this interpretation, the cardiac output does not determine the work rate. Rather the level to which the cardiac output rises is determined by the passive cardiovascular response to the oxygen demands of the tissues. This demand is in turn determined by the motor cortex as part of a complex feed-forward control mechanism. This is the CGM. Thus if the cardiac output is low at exhaustion, it is because the level of skeletal muscle recruitment is also low. This is the key interpretation that devotees of the Hill model have great difficulty understanding.

The VO2MAX and the Central Governor 91

Fourth Disproven Prediction

All available motor units are never activated in the exercising limbs at exhaustion. The fourth absolute requirement of the A.V. Hill model is that complete recruitment of all available motor units in the active limbs must occur some time prior to the development of exhaustion. For unless there is complete skeletal muscle recruitment at exhaustion during voluntary exercise, the central nervous system must be regulating that performance. For the clear prediction of the A.V. Hill model must be that as each motor unit becomes fatigued, the brain is forced to recruit additional units to sustain the activity. Ultimately when fatigue develops in the final motor unit recruited, the force output of the active muscles must also fall causing the exercise to terminate. In contrast, the CGM predicts that motor unit recruitment is regulated and never maximal so that exercise always terminates before there is a maximal skeletal muscle recruitment. Already in 1997 Sloniger and colleagues [46, 47] showed that muscle activation was not maximal in any of the major lower limb muscle groups at exhaustion during maximal horizontal or uphill running. This has since been confirmed in a study [48] which found that in none of the lower limb muscle groups was muscle activation at exhaustion during a

VO2max test more than about 70% of that achieved during a short bout of maximal sprint cycling (Figure 10). 24

20 Brain recruitment 18

) 16

1 - 14

(L.min 12 Cardiac output Cardiac

0 0 100 150 200 250 300 350 Workrate

Hill Model Central Governor Model

Figure 9. The Hill model predicts that it is the increase in cardiac output (A) that produces the increase in work rate (B) that occurs during progressive exercise to exhaustion. In contrast the Central Governor Model predicts that an increased motor command from the brain determines the increase in work rate that occurs during this form of exercise. The greater power output produced by the increased number of motor units that are activated in the exercising limbs, increases the blood and oxygen demands of the active skeletal muscles. As a consequence the cardiac output rises (C). 92 Timothy David Noakes

100 VM RF VL BF MG LG Mean EMG 90

EMG activity EMG (% during cycling) sprint 10

0 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3 Trials (day 1-3)

Figure 10. The study of Albertus[48] showed that the level of skeletal muscle recruitment in 6 different muscle groups during VO2max testing averaged about 50% of that achieved during a short burst of maximal cycling exercise. VM vastus medialis; RF rectus femoris; VL vastus lateralis; BF biceps femoris; MG medial gastrocnemius; LG lateral gastrocnemius; EMG electromyography.

Figure 11. The Hill model requires that the 4-fold higher “maximal” power output during a Wingate

“Anaerobic” test (2000W) than during a VO2max test (400W), must be due to 4-fold increase in muscle contractility without any increase in skeletal muscle recruitment. In contrast the Central Governor Model predicts that this increase in “maximal” power output is more likely explained by a much greater level of skeletal muscle recruitment during the Wingate “Anaerobic” test than during the VO2max test with perhaps a small change in skeletal muscle contractility. The VO2MAX and the Central Governor 93

Figure 11 depicts the explanations provided by either the A.V. Hill model or the CGM of the factors explaining exercise performance during either short duration exercise of very high intensity or during a VO2max test. The A.V. Hill model predicts that at the point of exhaustion during the VO2max test all motor units are active since the exercise must terminate only after “peripheral fatigue” has developed in all the available muscle fibers (motor units) in the exercising limbs. But this explanation seems unlikely since there are no known mechanisms by which skeletal muscle fibers can increase their contractility fourfold. Nor would it seem logical that this contractility “reserve” is activated only during “anaerobic” exercise of very short duration and not during more prolonged maximal “aerobic” exercise. In contrast, the CGM predicts that a fourfold increase in power generation can occur as a result of increased motor unit recruitment with some increase in skeletal muscle contractility. Thus to explain the approximately fourfold greater power output during maximal exercise of short duration, for example during the Wingate “anaerobic” test, than during a VO2max test, the Hill model requires that each contracting muscle fiber must be able to increase its power output fourfold. This can only be achieved with a fourfold increase in the contractility (Chapter 1) of each cross-bridge cycle. Indeed the unpublished results from our laboratory showed that EMG activity, our measure of the extent of skeletal muscle recruitment, rose as a linear function of power output during a progressive exercise test for the measurement of VO2max (Figure 12). But exercise terminated when EMG activity was less than about 60% of that achieved during a maximal voluntary contraction. But when subjects performed short bouts of exercise lasting between 10 and 20 seconds at progressively higher power outputs beginning at the power output at which they terminated the VO2max test, this linear increase in EMG activity continued up to the highest power output that these subjects were able to sustain for 10-20 seconds (Figure 12). This is not a novel finding. In his textbook [49], Enoka includes a figure (Figure 13) which also shows that only about 50% of the available motor neuron pool is activated during running whereas close to 100% of the motor neuron pool is active during a vertical jump. Thus all these findings confirm that skeletal muscle recruitment is submaximal during the

VO2max test, a finding which is completely incompatible with the A.V. Hill model. Indeed another interesting paradox in the exercise sciences is the explanation of what constitutes “maximal” exercise. Figure 14 explains this phenomenon. The “maximal” work rate achieved during a VO2max test in an elite cyclist might be 600W; the same athlete may be able to sustain a power output of about 2000W for a brief period during a Wingate “anaerobic” test, and perhaps an even greater power output during a vertical jump. According to the Hill model, the power output of 600W represents “maximal” exercise whereas the power output achieved during the Wingate test represents “supramaximal” exercise. But the term supramaximal is specious since by definition an exercise intensity cannot be maximal if there is another higher intensity that can also be sustained. The source of this error is the definition of the VO2max test as a maximal test which it is not since it does not activate 100% of the available force-producing elements in the exercising limbs (Figures 10 & 12)..

94 Timothy David Noakes

1.6

1.5 VO2max testing 1.4 Discontinuous testing 1.3 1.2 1.1 1.0 0.9 60% increase 0.8 0.7

0.6 iEMG (% (% iEMGMVC) 0.5 0.4 0.3 0.2 Slopes not significantly 0.1 different (P = 0.35) 0.0 200 300 400 500 600 700 800 900 Power output (W) 1.2 VO max testing 1.1 2 Slopes not significantly Discontinuous testing different (P = 0.80) 1.0

0.9

0.8

0.7

0.6

iEMG (% (% iEMGMVC) 0.5

0.4

0.3

0.2

0.1 200 300 400 500 600 700 800 900 Power output (W)

Figure 12. EMG activity (as a measure of skeletal muscle recruitment) rose as a linear function of the increasing work rate beyond that at which the VO2max was achieved in both the Vastus Medialis (top panel) and Vastus Lateralis (bottom panel) muscles. These data confirm that skeletal muscle activation is not maximal during VO2max testing (as is required by the Hill model).

The VO2MAX and the Central Governor 95

100 Vertical Slow twitch muscle fibers jump 90 Fast twitch oxidative muscle fibers 80 Fast twitch glycolytic muscle fibers

70 )

60 (W 50

40 Power Power 30

20 Run 10 Jog 0 0 50 100 Motor neuron pool recruitment (% total number)

Figure 13. The textbook of Enoka [49] includes a figure showing that running requires the activation of less than about 50% of the available motor neuron pool in the exercising skeletal muscles.

Power (Watts) >200% 100% Reserve Reserve

90 Vertical 2400 Vertical jump jump

80 2000 maximal Wingate Wingate - “Anaerobic” “Anaerobic” exercise

test test Supra 100% 60 600

VO2max test VO2max test

(A.V. Hill Model) Hill (A.V.

Intensity of Effort (%) of Effort Intensity

(Central Governor Model) Governor (Central Maximal exercise Maximal

Extent of skeletal muscle recruitment (%) recruitment muscle skeletal of Extent 0

Figure 14. According to the traditional Hill model any power output (exercise intensity) greater than that at which the VO2max is achieved, for example during the Wingate “Anaerobic” test or during a vertical jump, is “supramaximal” (right panel). But this term is specious since there is no intensity that can be higher than maximal, just as there is no state more dead than simply dead. But if all exercise intensities (power outputs) are graded according to the extent of skeletal muscle recruitment (left panel), then this specious term can be removed from the exercise science vernacular. Note that even a vertical jump does not recruit all the available motor units in the lower limbs; rather there is always some reserve capacity. 96 Timothy David Noakes

Figure 14 shows that in terms of skeletal muscle recruitment, the peak work rate of 600W achieved during the VO2max test occurs at a submaximal level of skeletal muscle recruitment. Similarly the work rate of 2000W is achieved at a higher but still submaximal level of skeletal muscle recruitment. When these work rates are compared on a scale of the level of skeletal muscle recruitment, it is clear that both are examples of submaximal exercise. Thus according to the CGM the intensity of any exercise bout should be related to the extent of skeletal muscle recruitment that is activated. Adopting this definition allows the specious term “supramaximal” to be removed from the accepted vernacular of our discipline.

Fifth Disproven Prediction

Fatigue does not always develop at the same level of fatiguing metabolites in the exercising limbs. The fifth absolute requirement of the Hill model is that fatigue in any form of exercise must always develop when the concentration of metabolites causing that fatigue reach concentrations that are identical regardless of the manner in which the fatigue was produced. But there are a number of studies showing that the originally-favored fatiguing metabolite, lactic acid, is not associated with fatigue and might indeed be ergogenic. For example, the study of the Nielsen et al. [50] came to the conclusion that the accumulation of lactic acid protects against muscular fatigue so that: "In contrast to the often stated role of lactic acid as a cause of muscular fatigue, lactic acid may protect against fatigue”. Many others have now come to the same conclusion [24]. In fact the unexplained paradox of the Hill model is that lactic acid needs to act selectively to impair the function of skeletal muscle whilst leaving the function of the heart and the respiratory muscles unaffected. It seems improbable that a substance that is supposedly toxic to one type of muscle can be the premier fuel for another, specifically the myocardium. This is a paradox that no one has yet challenged. The “lactate paradox of high altitude” is perhaps the best example of an exercise condition in which exercise terminates at low blood lactate concentrations. According to one respected scientist "... the presence of the Lactate Paradox during maximal exercise at altitude is one of the strongest demonstrations of a central limitation to exercise performance"[51]. It seems more probable that the choice to either stop or to slow down during exercise is made on the basis of a complex brain decision that is influenced by a number of factors one of which might indeed be the concentration of lactate in the muscles. But it is clear that lactate does not act directly in the muscles to cause fatigue as is required by the A.V. Hill model.

Sixth Disproven Prediction

The final absolute requirement of the A.V. Hill model is that fatigue must always be absolute. Yet the reality is that athletes speed up at the end of exercise (Figure 9 in Chapter 1), the classic “endspurt”, so that they cannot be absolutely fatigued. This phenomenon of the end spurt poses real problems for exercise scientists for as described in Chapter 1, it shows that our current definition of fatigue must be wrong. For the athlete‟s ability to speed up immediately prior to the termination of exercise proves that she was not fatigued according to the definition which holds that fatigue is present only when it is no longer possible to sustain The VO2MAX and the Central Governor 97 the desired workrate. Thus according to this definition any athlete able to develop an “endspurt” is by definition not fatigued. According to the CGM, the endspurt occurs because of an increase in skeletal muscle recruitment, perhaps associated with some increase in skeletal muscle contractility, whereas fatigue is purely an emotion [52] that is used to insure that athletes do not overexert themselves thereby threatening their homeostasis.

SUMMARY

The evidence presented here suggests that the VO2max test is a submaximal test that terminates at less than 100% of skeletal muscle recruitment.

The protected variable that triggers the anticipatory termination of the VO2 max test is currently unknown but may well relate to changes in blood flow to, or oxygenation of the brain [53, 54]. At high rates of respiratory ventilation, the most likely protected variable is cerebral (not myocardial or skeletal muscle) oxygenation. This is because at high rates of ventilation the carbon dioxide concentration in the blood falls and this is likely to induce cerebral vasoconstriction. This will reduce blood flow perhaps to critical parts of the brain, possibly inducing the desire to terminate the exercise. We also propose that the exercise intensity should be defined relative to the percentage of motor units that are recruited in the exercising limbs (Figure 14). This removes the specious term “supramaximal” from the vernacular.

Finally, since the VO2max test is “brainless”, it will likely have little value in the prediction of performance in those athletic events that requires some contribution from the athlete‟s brain. Instead what defines the really outstanding athletes is their ability to perform a devastating end spurt. It is not clear how the VO2max test can predict each athlete‟s ability to perform such an endspurt. Thus my interpretation is that the Hill model has become a fabulous fable. It is far more likely that the brain regulates exercise performance specifically to prevent the catastrophic metabolic failure that Professor Hill and his scientific progeny believe “limits” exercise performance.

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